The vascular bed as the primary target in the destruction of skin grafts by antiserum. II. Loss of sensitivity to antiserum in long-term xenografts of skin.
Rat skin that survives for long periods of time on immunosuppressed mice becomes resistant to anti-graft serum and remains so for as long as it survives. When long-standing grafts are removed and placed on new immunosuppressed mice, they remain resistant to antiserum for as long as they survive. The acquired resistance to antiserum seems, therefore, to be due to changes in the grafts rather than to changes in their hosts. Furthermore, it was found that the acquisition of resistance is correlated with replacement of graft endothelium by host cells, as demonstrated by the use of immunofluorescent techniques in conjunction with mouse anti-rat serum and rat anti-mouse serum. Evidently, humoral antibodies are able to cause acute damage to skin grafts, and presumably to grafts to other organized tissues, only if they react with antigens of graft endothelium. Long-term grafts that are retransplanted to their original donors or to rats syngeneic with those donors are in most cases rejected, whereas 14-d-old grafts similarly regrafted are in no case rejected. Apparently, the responses of the secondary recipients to the mouse endothelial antigens in long-term grafts lead to destruction of the entire grafts. When long-standing rat skin xenografts are removed and placed on untreated mice syngeneic with the primary hosts, they are in every case rejected, although they survive slightly longer than skin taken directly from rat donors. Rejection is accompanied by a mononuclear infiltrate and is qualitatively indistinguishable from the rejection of freshly prepared rat skin. Clearly, sensitized cells are more efficient than humoral antibody in destroying grafted tissues.
D000818:Animals; D003176:Complement C3; D006084:Graft Rejection; D006085:Graft Survival; D007106:Immune Sera / Q000494:pharmacology; D007136:Immunoglobulins / Q000008:administration & dosage; D007165:Immunosuppression Therapy; D008134:Long-Term Care; D051379:Mice; D008805:Mice, Inbred A; D011817:Rabbits; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012867:Skin / Q000098:blood supply; D016038:Skin Transplantation; D014183:Transplantation, Heterologous
D003176:Complement C3; D007106:Immune Sera; D007136:Immunoglobulins